Haemophilus influenzae is responsible for a number of local and invasive diseases in adults and children. There are six serotypes of H. influenzae which are defined by their capsular polysaccharide and designated a-f. In children, H. influenzae type b (Hib) causes 95 to 96% of invasive disease such as meningitis, epiglottitis and septicemia, and in adults Hib is responsible for 50% of invasive disease. Non-encapsulated or nontypable H. influenzae (NTHi) are a major cause of otitis media, bacteremia, chronic bronchitis and pneumonia. Of the other serotypes, H. influenzae types a, d, e and f have been associated with invasive disease at low frequencies. Vaccines based upon H. influenzae type b capsular polysaccharide conjugated to diphtheria toxoid (Ref. 1, Throughout this application, various references are referred to in parenthesis to more fully describe the state of the art to which this invention pertains. Full bibliographic information for each citation is found at the end of the specification, immediately preceding the claims. The disclosures of these references are hereby incorporated by reference into the present disclosure), tetanus toxoid (Ref. 2 and U.S. Pat. No. 4,496,538), or Neisseria meningitidis outer membrane protein (Ref. 3) have been effective in reducing H. influenzae type b-induced meningitis, but not NTHi-induced disease (Ref. 4).
Otitis media is the most common illness of early childhood with 60 to 70% of all children of less than 2 years of age experiencing between one and three ear infections. Chronic otitis media is responsible for hearing, speech and cognitive impairments in children. H. influenzae infections account for about 30% of the cases of acute otitis media and about 60% of chronic otitis media. In the United States alone, treatment of otitis media costs between 1 and 2 billion dollars per year for antibiotics and surgical procedures such as tonsillectomies, adenoidectomies and insertion of tympanostomy tubes. Furthermore, many of the causative organisms of otitis media are becoming resistant to antibiotic treatment. An effective prophylactic vaccine against otitis media is thus desirable. Non-typable strains of H. influenzae are also important pathogens responsible for pneumonia in the elderly and other individuals who are particularly susceptible to respiratory infections. There is thus a need for antigens from H. influenzae which are useful as components in immunogenic preparations that provide protection against the many serotypes of H. influenzae. Escherichia coli and H. influenzae are both facultative anaerobes. E. coli can derive energy for anaerobic growth by anaerobic respiration, utilizing substrates such as fumarate, nitrate, trimethylamine N-oxide (TMAO) and dimethylsulphoxide (DMSO). The anaerobic growth of E. coli on DMSO, TMAO, fumarate or methionine sulphoxide results in the induction of a membrane-bound molybdoenzyme catalysing the reduction of DMSO to dimethylsulphide (Ref. 5). The E. coli dimethylsulfoxide reductase enzyme is a complex of three proteins, namely DMS A, DMS B, and DMS C. The 87.4 kDa DMS A protein is the catalytic subunit which contains the non-covalently bound molybdopterin co-factor. The 23.1 kDa DMS B subunit is involved in electron transport and has homology to the (4Fe-4S) ferredoxins. The hydrophobic 30.8 kDa DMS C subunit anchors the complex in the cytoplasmic membrane. The E. coli dimethylsulphoxide reductase protein complex is encoded on an operon, dmsABC (Ref. 6). It would be desirable to provide the sequence of the DNA molecule that encodes a dimethylsulfoxide reductase enzyme of a strain of Haemophilus or an individual subunit or a fragment or an analog of the dimethylsulfoxide reductase enzyme and vectors containing such sequences for diagnosis, immunization and the generation of diagnostic and immunological reagents.